AutoGVP: a dockerized workflow integrating ClinVar and InterVar germline sequence variant classification.

SUMMARY: With the increasing rates of exome and whole genome sequencing, the ability to classify large sets of germline sequencing variants using up-to-date American College of Medical Genetics-Association for Molecular Pathology (ACMG-AMP) criteria is crucial. Here, we present Automated Germline Variant Pathogenicity (AutoGVP), a tool that integrates germline variant pathogenicity annotations from ClinVar and sequence variant classifications from a modified version of InterVar (PVS1 strength adjustments, removal of PP5/BP6). This tool facilitates large-scale, clinically focused classification of germline sequence variants in a research setting. AVAILABILITY AND IMPLEMENTATION: AutoGVP is an open source dockerized workflow implemented in R and freely available on GitHub at https://github.com/diskin-lab-chop/AutoGVP.

Genomic uncertainty and genetic counsellors' professional authority.

Genomic tests regularly produce Variants of Uncertain Significance (VUS), mutations of which currently little is known but may turn out to be disease-causing. The communication of such variants in the United States is typically delegated to genetic counsellors. Based on in-depth interviews, we examined this communication as an indicator of the genetic counsellor's professional status: did they take a subordinate position by reporting out the results as provided by laboratories or did they assert professional authority by interpreting and possibly reducing the uncertainty of VUS results? We found that genetic counsellors put their professional spin on VUS results and they prepared patients for the full range of possible interpretations by normalising the existence of VUS results; intervened in the ecology of testing laboratories to stack the deck in favour of the expected results; and conducted their own research to reclassify a VUS. They marshalled organisational, technical, scientific and communication expertise to ease the sting of uncertainty but were ultimately limited by their role in the counselling encounter rather than in the basic research or laboratory community. We concluded that genetic counsellors use uncertainty to assert professional authority that interpreted genetic test results in light of the patient's symptoms and risk profile and uncertainty tolerance.

Botulinum Neurotoxin A4 Has a 1000-Fold Reduced Potency Due to Three Single Amino Acid Alterations in the Protein Receptor Binding Domain.

Botulinum neurotoxin subtype A4 (BoNT/A4) is ~1000-fold less potent than BoNT/A1. This study addresses the basis for low BoNT/A4 potency. Utilizing BoNT/A1-A4 and BoNT/A4-A1 Light Chain-Heavy Chain (LC-HC) chimeras, HC-A4 was responsible for low BoNT/A4 potency. Earlier studies showed BoNT/A1-receptor binding domain (Hcc) bound a ß-strand peptide (556-564) and glycan-N559 within Luminal Domain 4 (LD4) of SV2C, the BoNT/A protein receptor. Relative to BoNT/A1, the Hcc of BoNT/A4 possesses two amino acid variants (D1141 and N1142) within the ß-peptide binding interface and one amino acid variant (R1292) located near the SV2C glycan-N559. Introduction of BoNT/A4 ß-strand peptide variant (D1141 and N1142) into BoNT/A1 reduced toxin potency 30-fold, and additional introduction of the BoNT/A4 glycan-N559 variant (D1141, N1142, and R1292) further reduced toxin potency to approach BoNT/A4. While introduction of BoNT/A1 glycan-N559 variant (G1292) into BoNT/A4 did not alter toxin potency, additional introduction of BoNT/A1 ß-strand peptide variants (G1141, S1142, and G1292) resulted in potency approaching BoNT/A1 potency. Thus, outcomes from these functional and modeling studies indicate that in rodent models, disruption of Hcc -SV2C ß-peptide and -glycan-N559 interactions mediate low BoNT/A4 potency, while in human motor neurons, disruption of Hcc-SV2C ß-peptide alone mediates low BoNT/A4 potency, which link to a species-specific variation at SV2C563.

Detecting Selection on Segregating Gene Duplicates in a Population.

Gene duplication is a fundamental process that has the potential to drive phenotypic differences between populations and species. While evolutionarily neutral changes have the potential to affect phenotypes, detecting selection acting on gene duplicates can uncover cases of adaptive diversification. Existing methods to detect selection on duplicates work mostly inter-specifically and are based upon selection on coding sequence changes, here we present a method to detect selection directly on a copy number variant segregating in a population. The method relies upon expected relationships between allele (new duplication) age and frequency in the population dependent upon the effective population size. Using both a haploid and a diploid population with a Moran Model under several population sizes, the neutral baseline for copy number variants is established. The ability of the method to reject neutrality for duplicates with known age (measured in pairwise dS value) and frequency in the population is established through mathematical analysis and through simulations. Power is particularly good in the diploid case and with larger effective population sizes, as expected. With extension of this method to larger population sizes, this is a tool to analyze selection on copy number variants in any natural or experimentally evolving population. We have made an R package available at https://github.com/peterbchi/CNVSelectR/ which implements the method introduced here.

Advancing Research and Measurement on Fathering and Child Development.

Fathers are more than social accidents. Research has demonstrated that fathers matter to children's development. Despite noted progress, challenges remain on how best to conceptualize and assess fathering and father-child relationships. The current monograph is the result of an SRCD-sponsored meeting of fatherhood scholars brought together to discuss these challenges and make recommendations for best practices for incorporating fathers in studies on parenting and children's development. The first aim of this monograph was to provide a brief update on the current state of research on fathering and to lay out a developmental ecological systems perspective as a conceptual framework for understanding the different spaces fathers inhabit in their children's lives. Because there is wide variability in fathers' roles, the ecological systems perspective situates fathers, mothers, children, and other caregivers within an evolving network of interrelated social relationships in which children and their parents change over time and space (e.g., residence). The second aim was to present examples of empirical studies conducted by members of the international working group that highlighted different methods, data collection, and statistical analyses used to capture the variability in father-child relationships. The monograph ends with a commentary that elaborates on the ecological systems framework with a discussion of the broader macrosystem and social-contextual influences that impinge on fathers and their children. The collection of articles contributes to research on father-child relationships by advancing theory and presenting varied methods and analysis strategies that assist in understanding the father-child relationship and its impact on child development.

Self-perceived Coparenting of Nonresident Fathers: Scale Development and Validation.

This study reports on the development and validation of the Fatherhood Research and Practice Network coparenting perceptions scale for nonresident fathers. Although other measures of coparenting have been developed, this is the first measure developed specifically for low-income, nonresident fathers. Focus groups were conducted to determine various aspects of coparenting. Based on this, a scale was created and administered to 542 nonresident fathers. Participants also responded to items used to examine convergent and predictive validity (i.e., parental responsibility, contact with the mother, father self-efficacy and satisfaction, child behavior problems, and contact and engagement with the child). Factor analyses and reliability tests revealed three distinct and reliable perceived coparenting factors: undermining, alliance, and gatekeeping. Validity tests suggest substantial overlap between the undermining and alliance factors, though undermining was uniquely related to child behavior problems. The alliance and gatekeeping factors showed strong convergent validity and evidence for predictive validity. Taken together, results suggest this relatively short measure (11 items) taps into three coparenting dimensions significantly predictive of aspects of individual and family life.

'At times, I feel like I'm sinning': the paradoxical role of non-lesbian, gay, bisexual and transgender-affirming religion in the lives of behaviourally-bisexual Latino men.

In this paper, we examine non-lesbian, gay, bisexual and transgender-affirming religiosity among behaviourally-bisexual Latino men as it relates to sexual attitudes, experiences and behaviours. We asked how does religiosity correspond to masculine identities, sex roles and condom efficacy? And how might religiosity influence contexts of health risks? Data were analysed from a mixed-methods study of 142 behaviourally-bisexual Latino men, aged 18-60 years. Major findings include positive correlations between religiosity and (1) masculine ideologies, (2) internalised homonegativity, (3) less comfort with receptive sex, (4) low condom efficacy and (5) higher levels of loneliness and incidents of discriminatory events. Results are paired with illustrative, descriptive case studies from life history interviews. It is suggested that non-lesbian, gay, bisexual and transgender-affirming religiosity plays a paradoxical role in the lives of behaviourally-bisexual Latino men - on one hand, increasing internalised homonegativity and attendant health risks and, on the other, providing social support to members of a marginalised population.

High risk, mixed reward: Making genetic test results actionable in cardiology.

Professional organizations point to the underutilization of genetic testing in cardiology as a lack of genetic literacy. Yet, few studies have examined the interpretive work required from clinicians to make results clinically actionable. Based on interviews with twenty-nine cardiologists, we find that although genetic testing may provide epistemic closure by substantiating a suspected diagnosis at the molecular level, genetic testing often disrupted cardiologists' diagnostic inferential processes. These epistemic disruptions were not intrinsic to a particular genetic result type (positive, negative, or VUS), but arose from reconciling genetic results with the patient's symptoms and medical and family history. Drawing from the sociology of diagnosis and professional expertise, we examine how cardiologists resolved epistemic disruptions by either sidelining or repairing genetic test results. However, such attempts at making genetic test results actionable for diagnosis may not resolve epistemic disruptions. We argue that rather than clinicians lacking individual literacy, the limited uptake of genetic test results reflects a collective problem of gaps in the genetic knowledge base that leads to medical agnosis, or an inability to make sense of a patient's symptoms uncertainty, rather than diagnosis.

Cell Context is the third axis of synergy for the combination of ATR inhibition and cisplatin in Ewing sarcoma.

PURPOSE: The importance of cellular context to the synergy of DNA Damage Response (DDR) targeted agents is important for tumors with mutations in DDR pathways, but less well-established for tumors driven by oncogenic transcription factors. In this study, we exploit the widespread transcriptional dysregulation of the EWS-FLI1 transcription factor to identify an effective DDR targeted combination therapy for Ewing Sarcoma (ES). EXPERIMENTAL DESIGN: We used matrix drug screening to evaluate synergy between a DNA-PK inhibitor (M9831) or an ATR inhibitor (berzosertib) and chemotherapy. The combination of berzosertib and cisplatin was selected for broad synergy, mechanistically evaluated for ES selectivity, and optimized for in vivo schedule. RESULTS: Berzosertib combined with cisplatin demonstrates profound synergy in multiple ES cell lines at clinically achievable concentrations. The synergy is due to loss of expression of the ATR downstream target CHEK1, loss of cell cycle checkpoints, and mitotic catastrophe. Consistent with the goals of the project, EWS-FLI1 drives the expression of CHEK1 and five other ATR pathway members. The loss of CHEK1 expression is not due to transcriptional repression and instead caused by degradation coupled with suppression of protein translation. The profound synergy is realized in vivo with a novel optimized schedule of this combination in subsets of ES models leading to durable complete responses in 50% of animals bearing two different ES xenografts. CONCLUSION: These data exploit EWS-FLI1 driven alterations in cell context to broaden the therapeutic window of berzosertib and cisplatin to establish a promising combination therapy and a novel in vivo schedule.

Germline pathogenic variants in neuroblastoma patients are enriched in BARD1 and predict worse survival.

BACKGROUND: Neuroblastoma is an embryonal cancer of the developing sympathetic nervous system. The genetic contribution of rare pathogenic or likely pathogenic germline variants in patients without a family history remains unclear. METHODS: Germline DNA sequencing was performed on 786 neuroblastoma patients. The frequency of rare cancer predisposition gene pathogenic or likely pathogenic variants in patients was compared with 2 cancer-free control cohorts. Matched tumor DNA sequencing was evaluated for second hits, and germline DNA array data from 5585 neuroblastoma patients and 23 505 cancer-free control children were analyzed to identify rare germline copy number variants. Patients with germline pathogenic or likely pathogenic variants were compared with those without to test for association with clinical characteristics, tumor features, and survival. RESULTS: We observed 116 pathogenic or likely pathogenic variants involving 13.9% (109 of 786) of neuroblastoma patients, representing a statistically significant excess burden compared with cancer-free participants (odds ratio [OR] = 1.60, 95% confidence interval [CI] = 1.27 to 2.00). BARD1 harbored the most statistically significant enrichment of pathogenic or likely pathogenic variants (OR = 32.30, 95% CI = 6.44 to 310.35). Rare germline copy number variants disrupting BARD1 were identified in patients but absent in cancer-free participants (OR = 29.47, 95% CI = 1.52 to 570.70). Patients harboring a germline pathogenic or likely pathogenic variant had a worse overall survival compared with those without (P = 8.6 x 10-3). CONCLUSIONS: BARD1 is an important neuroblastoma predisposition gene harboring both common and rare germline pathogenic or likely pathogenic variations. The presence of any germline pathogenic or likely pathogenic variant in a cancer predisposition gene was independently predictive of worse overall survival. As centers move toward paired tumor-normal sequencing at diagnosis, efforts should be made to centralize data and provide an infrastructure to support cooperative longitudinal prospective studies of germline pathogenic variation.

AutoGVP: a dockerized workflow integrating ClinVar and InterVar germline sequence variant classification.

With the increasing rates of exome and whole genome sequencing, the ability to classify large sets of germline sequencing variants using up-to-date American College of Medical Genetics - Association for Molecular Pathology (ACMG-AMP) criteria is crucial. Here, we present Automated Germline Variant Pathogenicity (AutoGVP), a tool that integrates germline variant pathogenicity annotations from ClinVar and sequence variant classifications from a modified version of InterVar (PVS1 strength adjustments, removal of PP5/BP6). This tool facilitates large-scale, clinically-focused classification of germline sequence variants in a research setting.

Alternative lengthening of telomeres (ALT) in pediatric high-grade gliomas can occur without ATRX mutation and is enriched in patients with pathogenic germline mismatch repair (MMR) variants.

BACKGROUND: To achieve replicative immortality, most cancers develop a telomere maintenance mechanism, such as reactivation of telomerase or alternative lengthening of telomeres (ALT). There are limited data on the prevalence and clinical significance of ALT in pediatric brain tumors, and ALT-directed therapy is not available. METHODS: We performed C-circle analysis (CCA) on 579 pediatric brain tumors that had corresponding tumor/normal whole genome sequencing through the Open Pediatric Brain Tumor Atlas (OpenPBTA). We detected ALT in 6.9% (n = 40/579) of these tumors and completed additional validation by ultrabright telomeric foci in situ on a subset of these tumors. We used CCA to validate TelomereHunter for computational prediction of ALT status and focus subsequent analyses on pediatric high-grade gliomas (pHGGs) Finally, we examined whether ALT is associated with recurrent somatic or germline alterations. RESULTS: ALT is common in pHGGs (n = 24/63, 38.1%), but occurs infrequently in other pediatric brain tumors (<3%). Somatic ATRX mutations occur in 50% of ALT+ pHGGs and in 30% of ALT- pHGGs. Rare pathogenic germline variants in mismatch repair (MMR) genes are significantly associated with an increased occurrence of ALT. CONCLUSIONS: We demonstrate that ATRX is mutated in only a subset of ALT+ pHGGs, suggesting other mechanisms of ATRX loss of function or alterations in other genes may be associated with the development of ALT in these patients. We show that germline variants in MMR are associated with the development of ALT in patients with pHGG.

Germline pathogenic variants in 786 neuroblastoma patients.

Importance: Neuroblastoma accounts for 12% of childhood cancer deaths. The genetic contribution of rare pathogenic germline variation in patients without a family history remains unclear. Objective: To define the prevalence, spectrum, and clinical significance of pathogenic germline variation in cancer predisposition genes (CPGs) in neuroblastoma patients. Design Setting and Participants: Germline DNA sequencing was performed on the peripheral blood from 786 neuroblastoma patients unselected for family history. Rare variants mapping to CPGs were evaluated for pathogenicity and the percentage of cases harboring pathogenic (P) or likely pathogenic (LP) variants was quantified. The frequency of CPG P-LP variants in neuroblastoma cases was compared to two distinct cancer-free control cohorts to assess enrichment. Matched tumor DNA sequencing was evaluated for "second hits" at CPGs and germline DNA array data from 5,585 neuroblastoma cases and 23,505 cancer-free control children was analyzed to identify rare germline copy number variants (CNVs) affecting genes with an excess burden of P-LP variants in neuroblastoma. Neuroblastoma patients with germline P-LP variants were compared to those without P-LP variants to test for association with clinical characteristics, tumor features, and patient survival. Main Outcomes and Measures: Rare variant prevalence, pathogenicity, enrichment, and association with clinical characteristics, tumor features, and patient survival. Results: We observed 116 P-LP variants in CPGs involving 13.9% (109/786) of patients, representing a significant excess burden of P-LP variants compared to controls (9.1%; P = 5.14 × 10-5, Odds Ratio: 1.60, 95% confidence interval: 1.27-2.00). BARD1 harbored the most significant burden of P-LP variants compared to controls (1.0% vs. 0.03%; P = 8.18 × 10-7; Odds Ratio: 32.30, 95% confidence interval: 6.44-310.35). Rare germline CNVs disrupting BARD1 were also identified in neuroblastoma patients (0.05%) but absent in controls (P = 7.08 × 10-3; Odds Ratio: 29.47, 95% confidence interval: 1.52 - 570.70). Overall, P-LP variants in DNA repair genes in this study were enriched in cases compared to controls (8.1% vs. 5.7%; P = 0.01; Odds Ratio: 1.45, 95% confidence interval: 1.08-1.92). Neuroblastoma patients harboring a germline P-LP variant had a worse overall survival when compared to patients without P-LP variants (P = 8.6 × 10-3), and this remained significant in a multivariate Cox proportional-hazards model (P = 0.01). Conclusions and Relevance: Neuroblastoma patients harboring germline P-LP variants in CPGs have worse overall survival and BARD1 is an important predisposition gene affected by both common and rare pathogenic variation. Germline sequencing should be performed for all neuroblastoma patients at diagnosis to inform genetic counseling and support future longitudinal and mechanistic studies. Patients with a germline P-LP variant should be closely monitored, regardless of risk group assignment.

Lurbinectedin Inhibits the EWS-WT1 Transcription Factor in Desmoplastic Small Round Cell Tumor.

Desmoplastic small round cell tumor (DSRCT) is a rare pediatric sarcoma with poor overall survival. This tumor is absolutely dependent on the continued expression and activity of its defining molecular lesion, the EWS-WT1 transcription factor. Unfortunately, the therapeutic targeting of transcription factors is challenging, and there is a critical need to identify compounds that inhibit EWS-WT1. Here we show that the compound lurbinectedin inhibits EWS-WT1 by redistributing the protein within the nucleus to the nucleolus. This nucleolar redistribution interferes with the activity of EWS-WT1 to reverse the expression of over 70% of the transcriptome. In addition, the compound blocks the expression of the EWS-WT1 fusion protein to inhibit cell proliferation at the lowest GI50 ever reported for this compound in any cell type. The effects occur at concentrations that are easily achievable in the clinic and translate to the in vivo setting to cause tumor regressions in multiple mice in a xenograft and PDX model of DSRCT. Importantly, this mechanism of nucleolar redistribution is also seen with wild-type EWSR1 and the related fusion protein EWS-FLI1. This provides evidence for a "class effect" for the more than 18 tumors driven by EWSR1 fusion proteins. More importantly, the data establish lurbinectedin as a promising clinical candidate for DSRCT.

Mushroom bodies enhance initial motor activity in Drosophila.

The central body (or central complex, CCX) and the mushroom bodies (MBs) are brain structures in most insect phyla that have been shown to influence aspects of locomotion. The CCX regulates motor coordination and enhances activity while MBs have, thus far, been shown to suppress motor activity levels measured over time intervals ranging from hours to weeks. In this report, we investigate MB involvement in motor behavior during the initial stages (15 minutes) of walking in Buridan's paradigm. We measured aspects of walking in flies that had MB lesions induced by mutations in six different genes and by chemical ablation. All tested flies were later examined histologically to assess MB neuroanatomy. Mutant strains with MB structural defects were generally less active in walking than wild-type flies. Most mutants in which MBs were also ablated with hydroxyurea (HU) showed additional activity decrements. Variation in measures of velocity and orientation to landmarks among wild-type and mutant flies was attributed to pleiotropy, rather than to MB lesions. We conclude that MBs upregulate activity during the initial stages of walking, but suppress activity thereafter. An MB influence on decision making has been shown in a wide range of complex behaviors. We suggest that MBs provide appropriate contextual information to motor output systems in the brain, indirectly fine tuning walking by modifying the quantity (i.e., activity) of behavior.

Brain GABA levels in patients with bipolar disorder.

PURPOSE: A growing body of research supports an important role for GABA in the pathophysiology of bipolar and other mood disorders. The purpose of the current study was to directly examine brain GABA levels in a clinical sample of bipolar patients. GENERAL METHODS: We used magnetic resonance spectroscopy (MRS) to examine whole brain and regional GABA, glutamate and glutamine in 13 patients with bipolar disorder compared to a matched group of 11 healthy controls. FINDINGS: There were no significant differences in GABA, glutamate or glutamine between patients and controls. CONCLUSIONS: Further research is needed to better characterize the GABAergic and glutamatergic effects of pharmacotherapy, anxiety comorbidity and clinical state in bipolar disorder.

Heterozygosity and asymmetry: Ectodysplasin as a form of genetic stress in marine threespine stickleback.

Genome-wide heterozygosity has long been hypothesized to play a role in buffering organisms against developmental perturbations, potentially resulting in increased symmetry. If true, this could in part explain the maintenance of standing genetic variation in wild populations. Marine threespine sticklebacks (Gasterosteus aculeatus) were sampled across their eastern Pacific coastal distribution from Alaska to California and variations in asymmetry for both structural and nonstructural armor traits (lateral plates) were assessed. Structural plates consistently showed less asymmetry than nonstructural plates, but standardized measures of heterozygosity were not correlated with the extent of asymmetry expressed by a fish. Fish that were heterozygous for the major-effect gene controlling lateral plate variation (Ectodysplasin) had higher occurrences of asymmetry, even when the individuals were phenotypically fully plated. Collectively, this suggests that heterozygosity at a major-effect locus can have a greater impact on asymmetry than heterozygosity sampled across the genome.

High-field MRS study of GABA, glutamate and glutamine in social anxiety disorder: response to treatment with levetiracetam.

OBJECTIVE: Abnormalities in brain gamma-aminobutyric acid (GABA) and glutamate may be relevant to the underlying pathophysiology of anxiety disorders including social anxiety disorder (SAD). METHODS: We used proton magnetic resonance spectroscopy (pMRS) to examine whole brain and regional GABA, glutamate and glutamine in patients (N=10) with SAD at baseline compared to a matched group of healthy controls (HC), and changes following 8 weeks of pharmacotherapy with levetiracetam. RESULTS: For SAD subjects, there were significantly higher whole brain levels of glutamate and glutamine, though no significant differences in GABA. In the thalamus, glutamine was higher and GABA lower for SAD subjects. There was a significant reduction in thalamic glutamine with levetiracetam treatment. CONCLUSION: Our findings provide preliminary support for impaired GABAergic and overactive glutamatergic function in social anxiety disorder and the potential relevance of changes in these systems for the anxiolytic response to levetiracetam.

Aripiprazole as augmentation treatment of refractory generalized anxiety disorder and panic disorder.

INTRODUCTION: Individuals with anxiety disorders often remain symptomatic despite treatment with a first-line pharmacologic agent. More research examining pharmacotherapy augmentation strategies to improve outcomes is needed. METHODS: In an 8-week, open-label, prospective augmentation study, we examined the efficacy and tolerability of the novel antipsychotic agent aripiprazole for adult outpatients with generalized anxiety disorder (n=13) or panic disorder (n=10) who remained symptomatic despite treatment for at least 8 weeks with an adequate (or maximally tolerated) dose of typical pharmacotherapy. RESULTS: Aripiprazole augmentation was associated with a significant reduction in Clinical Global Impressions-Severity scores (paired t=4.41, df=22, P<.001) in the intent-to-treat sample of 23 individuals. Three subjects (13%) discontinued due to sedation, chest discomfort, and restlessness, respectively. CONCLUSION: These data provide preliminary evidence that aripiprazole may be a useful augmentation strategy for individuals with generalized anxiety disorder or panic disorder who show a limited response to initial pharmacotherapy.

Father-child closeness and conflict: Validating measures for nonresident fathers.

A child's relationship with his or her nonresident father has been found to be related to that child's development in important ways. However, validated measures of the relationship between nonresident fathers and their children are rare, particularly for low-income nonresident fathers. To provide guidance for researchers and practitioners evaluating nonresident fatherhood programs, this study uses a sample of 420 primarily low-income nonresident fathers to examine the reliability, convergent validity, and predictive validity of measures of father-child closeness and conflict contained in the Child-Parent Relationship Scale-Short Form (CPRS-SF). Validity was examined across 3 child age groups: preschool, middle childhood, and adolescence. The CPRS-SF closeness scale demonstrated measurement equivalence across time (conflict did not) and had excellent reliability and validity. Compared to the closeness scale, the CPRS-SF conflict scale was related to fewer validity items but still showed both convergent and predictive validity, including predicting child behavior problems (which the closeness scale did not). Both the closeness and conflict scales are recommended for use with low-income nonresident fathers. Age differences in validity findings are discussed. (PsycINFO Database Record